Respiratory muscle fatigue and mechanical ventilator dependency contribute significantly to the morbidity and mortality of patients suffereing from chronic pulmonary disease. The diaphragm is the principal muscle of inspiration and the only skeletal muscle considered to be a vital organ. Yet, the adaptive capability of the diaphragm to varying amounts of respiratory work has received little investigative attention. The aim of this project will be to define the biochemical characteristics and mechanisms by which the rat diaphragm adapts to overuse and disuse; to determine if the adaptation to disuse is preventable or reversible and to gain new insight into the biochemical limitations responsible for respiratory muscle fatigue and failure. This will be accomplished employing experimental models already in use by this applicant. Specifically, surgically implanted tracheal resistors are used to study the diaphragm's response to endurance training and prolonged mechanical ventilation is used to study the diaphragm's response to disuse. The adaptive response of the diaphragm will be analyzed using measurements of fiber type, contractility and endurance as well as functional biochemical indices of whole muscle and mitochondria oxidative capacity, Preliminary data indicates that rat diaphragm muscle does adapt to resistance training with hypertrophy and adapts to mechanical ventilation with atrophy.